JP4782344B2 - ベンザゾール誘導体と、そのjnkモジュレータとしての利用法 - Google Patents
ベンザゾール誘導体と、そのjnkモジュレータとしての利用法 Download PDFInfo
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- JP4782344B2 JP4782344B2 JP2001549390A JP2001549390A JP4782344B2 JP 4782344 B2 JP4782344 B2 JP 4782344B2 JP 2001549390 A JP2001549390 A JP 2001549390A JP 2001549390 A JP2001549390 A JP 2001549390A JP 4782344 B2 JP4782344 B2 JP 4782344B2
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- Prior art keywords
- substituted
- unsubstituted
- benzothiazol
- acetonitrile
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 66
- -1 nitro, sulfoxy, sulfonyl Chemical group 0.000 claims description 138
- 125000001072 heteroaryl group Chemical group 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 40
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 150000002431 hydrogen Chemical class 0.000 claims description 35
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000003107 substituted aryl group Chemical group 0.000 claims description 28
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 23
- 125000001302 tertiary amino group Chemical group 0.000 claims description 23
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000004442 acylamino group Chemical group 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 14
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 13
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 13
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229940124530 sulfonamide Drugs 0.000 claims description 8
- 150000003456 sulfonamides Chemical class 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 230000014509 gene expression Effects 0.000 claims description 6
- 150000003230 pyrimidines Chemical class 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 5
- PKNYJVSQHRVGTB-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-methoxypyrimidin-4-yl)acetonitrile Chemical compound COC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 PKNYJVSQHRVGTB-UHFFFAOYSA-N 0.000 claims description 4
- HHPADGYFHUJULV-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-pyrazol-1-ylpropylamino)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCCN1C=CC=N1 HHPADGYFHUJULV-UHFFFAOYSA-N 0.000 claims description 4
- FDPMHJTUFOTVTN-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-[[3-(trifluoromethyl)pyridin-2-yl]amino]ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC(F)(F)C1=CC=CN=C1NCCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 FDPMHJTUFOTVTN-UHFFFAOYSA-N 0.000 claims description 4
- OSXMTIFMYHFUHI-UHFFFAOYSA-N 4-[2-[[4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl]amino]ethyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 OSXMTIFMYHFUHI-UHFFFAOYSA-N 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
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- 201000006474 Brain Ischemia Diseases 0.000 claims description 3
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- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
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- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- FIOQJQAZLSDRKC-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(3-imidazol-1-ylpropylamino)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-(2-pyrrolidin-1-ylpyrimidin-4-yl)acetonitrile Chemical compound S1C(=NC2=C1C=CC=C2)C(C#N)C2=NC(=NC=C2)N2CCCC2.S2C(=NC1=C2C=CC=C1)C(C#N)C1=NC(=NC=C1)NCCCN1C=NC=C1 FIOQJQAZLSDRKC-UHFFFAOYSA-N 0.000 claims description 2
- LVNXDCHGOBMXPF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-(2-morpholin-4-ylpyrimidin-4-yl)acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N1CCOCC1.C1CN(C)CCN1C1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 LVNXDCHGOBMXPF-UHFFFAOYSA-N 0.000 claims description 2
- ADWOTXPHEKVNML-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(4-pyrazin-2-ylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-(4-pyrimidin-2-ylpiperazin-1-yl)pyrimidin-4-yl]acetonitrile Chemical compound N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1C1=CN=CC=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1C1=NC=CC=N1 ADWOTXPHEKVNML-UHFFFAOYSA-N 0.000 claims description 2
- ALFIAYHEMBNSLM-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(methylamino)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[4-(2-morpholin-4-ylethyl)piperazin-1-yl]pyrimidin-4-yl]acetonitrile Chemical compound CNC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1N(CC1)CCN1CCN1CCOCC1 ALFIAYHEMBNSLM-UHFFFAOYSA-N 0.000 claims description 2
- BDNCPOOPCBONJH-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-2-ylmethoxy)pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-(pyridin-4-ylmethoxy)pyrimidin-4-yl]acetonitrile Chemical compound N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccncc2)n1.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2ccccn2)n1 BDNCPOOPCBONJH-UHFFFAOYSA-N 0.000 claims description 2
- FLPWZPQPYWSABF-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(2-hydroxy-2-phenylethyl)amino]pyrimidin-4-yl]acetonitrile Chemical compound N=1C=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=NC=1NCC(O)C1=CC=CC=C1 FLPWZPQPYWSABF-UHFFFAOYSA-N 0.000 claims description 2
- LFATXMVRHOXIPK-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[(3-phenylphenyl)methoxy]pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[(3,4,5-trimethoxyphenyl)methoxy]pyrimidin-4-yl]acetonitrile Chemical compound COc1cc(COc2nccc(n2)C(C#N)c2nc3ccccc3s2)cc(OC)c1OC.N#CC(c1nc2ccccc2s1)c1ccnc(OCc2cccc(c2)-c2ccccc2)n1 LFATXMVRHOXIPK-UHFFFAOYSA-N 0.000 claims description 2
- VJWNKFBXQSTDQJ-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-fluorophenyl)ethylamino]pyrimidin-4-yl]acetonitrile 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(4-phenoxyphenyl)ethylamino]pyrimidin-4-yl]acetonitrile Chemical compound FC1=CC=CC(CCNC=2N=C(C=CN=2)C(C#N)C=2SC3=CC=CC=C3N=2)=C1.N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1NCCC(C=C1)=CC=C1OC1=CC=CC=C1 VJWNKFBXQSTDQJ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
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- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP99811207.2 | 1999-12-24 | ||
EP99811207A EP1110957A1 (en) | 1999-12-24 | 1999-12-24 | Benzazole derivatives and their use as JNK modulators |
PCT/EP2000/013006 WO2001047920A1 (en) | 1999-12-24 | 2000-12-20 | Benzazole derivatives and their use as jnk modulators |
Publications (2)
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JP2003519142A JP2003519142A (ja) | 2003-06-17 |
JP4782344B2 true JP4782344B2 (ja) | 2011-09-28 |
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JP2001549390A Expired - Lifetime JP4782344B2 (ja) | 1999-12-24 | 2000-12-20 | ベンザゾール誘導体と、そのjnkモジュレータとしての利用法 |
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EP (2) | EP1110957A1 (et) |
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CN (1) | CN1252067C (et) |
AR (1) | AR029215A1 (et) |
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AU (1) | AU780241B2 (et) |
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CA (1) | CA2394809C (et) |
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EA (1) | EA007152B1 (et) |
EE (1) | EE05456B1 (et) |
ES (1) | ES2206351T3 (et) |
HK (1) | HK1055730A1 (et) |
HR (1) | HRP20020496B1 (et) |
HU (1) | HU229625B1 (et) |
IL (2) | IL150346A0 (et) |
MX (1) | MXPA02006242A (et) |
NO (1) | NO323146B1 (et) |
NZ (1) | NZ519423A (et) |
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WO (1) | WO2001047920A1 (et) |
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